A new class of copper(II) nanohybrid solids, LCu(CH(3)COO)(2) and LCuCl(2), have been synthesized and characterized by transmission electron microscopy, dynamic light scattering, and IR spectroscopy, and have been found to be capped by a bis(benzimidazole) diamide ligand (L). The particle sizes of these nanohybrid solids were found to be in the ranges 5-10 and 60-70 nm, respectively. These nanohybrid solids were evaluated for their in vitro antimalarial activity against a chloroquine-sensitive isolate of Plasmodium falciparum (MRC 2). The interactions between these nanohybrid solids and plasmepsin II (an aspartic protease and a plausible novel target for antimalarial drug development), which is believed to be essential for hemoglobin degradation by the parasite, have been assayed by UV-vis spectroscopy and inhibition kinetics using Lineweaver-Burk plots. Our results suggest that these two compounds have antimalarial activities, and the IC(50) values (0.025-0.032 microg/ml) are similar to the IC(50) value of the standard drug chloroquine used in the bioassay. Lineweaver-Burk plots for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) show that the inhibition is competitive with respect to the substrate. The inhibition constants of LCu(CH(3)COO)(2) and LCuCl(2) were found to be 10 and 13 microM, respectively. The IC(50) values for inhibition of plasmepsin II by LCu(CH(3)COO)(2) and LCuCl(2) were found to be 14 and 17 microM, respectively. Copper(II) metal capped by a benzimidazole group, which resembles the histidine group of copper proteins (galactose oxidase, beta-hydroxylase), could provide a suitable anchoring site on the nanosurface and thus could be useful for inhibition of target enzymes via binding to the S1/S3 pocket of the enzyme hydrophobically. Both copper(II) nanohybrid solids were found to be nontoxic against human hepatocellular carcinoma cells and were highly selective for plasmepsin II versus human cathepsin D. The pivotal mechanism of antimalarial activity of these compounds via plasmepsin II inhibition in the P. falciparum malaria parasite is demonstrated.

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dGiardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O 2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, 1 H and 13 C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O 2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O 2 concentrations.

Never‐ending effort to develop new treatments for malaria, targeting the hemoglobin‐degradation in the food vacuole of the parasite is of particular interest because it appears to be critical for the erythrocytic stage parasite development. The Plasmodium aspartic proteinases plasmepsins and cysteine proteases falcipains have been shown to be the major hemoglobin‐degrading proteases and are proposed as the high priority drug targets by the World Health Organization for developing novel small molecules as inhibitors of hemoglobin degradation. In the present study, several piperidine and piperazine‐based chalcones were assessed for anti‐malarial activity against the chloroquine‐susceptible P. falciparum 3D7 strain and inhibition of plasmepsin II and falcipain‐2. Degradation of hemoglobin by falcipain‐2 in the presence or absence of inhibitors was also demonstrated by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis. The IC50 values of chalcones for cell growth inhibition were in the range of 1.60‐153.51 μM. IC50 values for cytotoxicity of selected chalcones against Michigan Cancer Foundation (MCF) 7 human breast adenocarcinoma cells were in the range of 8.46‐15.64 μM. Molecular docking studies revealed the binding orientation of these chalcones in the active sites of falcipain‐2. Our results clearly depict the advantage of these chalcones as they kill P. falciparum malaria parasite in culture, most likely via inhibition of falcipain.

Three new chiral phthalimides have been synthesized and characterized. Phthalimides (1-3) possess an acentric structure as revealed by structural investigation. Compounds 1 and 2 crystallize in an orthorhombic system with the space group P2 1 2 1 2 1 , however the monoclinic system with the chiral space group P2 1 is observed for 3. The presence of C-H … O hydrogen bonds in 1-3 facilitates the construction of several supramolecular structures. Helical structural motifs are also observed. The maximum value of hyperpolarizability (b), 159.9446 6 10 230 esu calculated for compound 3 is several times greater than that of urea. On the other hand 1 and 2 have hyperpolarizabilities of 10.8063 6 10 230 and 121.9519 6 10 230 esu, respectively. The polycrystalline samples of 1-3 were assessed for a secondharmonic generation response, which was found to be 8.8, 10.2 and 9.7 mV respectively. Further, compounds 1-3 showed d 33 values of 0.93, 1.97 and 1.88 pC N 21 respectively. The present investigation demonstrates chiral phthalimides as effective contenders for nonlinear optical and piezoelectric properties.